Objective: To investigate whether the inhibition of protein phosphatase 2A catalytic subunit Cα (PP2Acα) affects the malignant phenotype of gastric cancer cells and the expression of Wilms tumor 1 related protein (WTAP) in this progression. Methods: The Cancer Genome Atlas (TCGA) database was used to compare the expression of PP2Acα coding gene (PPP2CA) and WTAP in gastric cancer and normal tissues adjacent to the cancer; the kmplot website was used to analyze the relationship between PPP2CA, WTAP and the prognosis of gastric cancer; lentivirus-mediated short hair Card RNA (shRNA) was used to inhibit the expression of PP2Acα in gastric cancer cells, and then we extract RNA and protein for PCR and WB to detect the mRNA and protein expression of PPP2CA, WTAP; finally, we detect the inhibition of PP2Acα for the influences of gastric cancer cells phenotype in vitro and in vivo. Results: After inhibiting PP2Acα, it was found that the proliferation, migration and invasion capabilities of gastric cancer cells were enhanced, accompanied by a significant increase in the protein level of WTAP. Conclusion: Inhibition of PP2Acɑ promotes the malignant phenotype of gastric cancer cells, which may be achieved by high levels of WTAP.